WITS is a seminal study of perinatal HIV infection. It has a wide-ranging agenda seeking in-depth information from a large cohort of HIV infected women and their infants. The current Chicago WITS-I group includes the University of Illinois at Chicago, Northwestern University, Children's Memorial Hospital and Cook county Hospital. Chicago team members have contributed to the scientific collaborative agenda of the study, the development of procedures for the execution of the study nationally as well as locally, and have provided leadership in specific protocols and dissemination of results. They have also received other grant support for basic scientific and epidemiologic studies and clinical trials that interact with WITS and extends its scope. Through December 1992, the Chicago site enrolled 116 pregnant HIV infected women, 39 non-pregnant HIV infected women, and 79 infants. During the last year Northwestern University (including Children's Memorial Hospital) and Cook County Hospital started enrolling participants. For the last 6 months, the average Chicago enrollment has averaged 5.2 per month or 62 per year. Chicago also proposes adding University of Chicago as an additional site for WITS-II. Therefore, it is conservatively estimated that enrollment for year 1 of WITS-II will be 75, without taking into account an increase in seroprevalence. The seroprevalence of HIV infection in pregnancy by anonymous newborn survey in the State of Illinois increased 52% 1992 over the preceding year. Although Chicago has been a moderate seroprevalence area, these figures suggest an important surge in the epidemic of perinatal HIV infection. The Chicago WITS site will be in a unique position of monitoring the changing dynamics of the epidemic. The Chicago group will continue to contribute quality data and innovative ideas. 94% of study visits were completed on time, 91% of participants originally enrolled have continued in the study, and greater than 92% of historical, physical examination and demographic forms are complete or will be competed shortly. More than 90% of indicated laboratory studies were obtained, including 91% of HIV cultures and 92% of lymphocyte phenotyping studies. To enhance the scientific value of WITS-II, the Chicago team proposes several developmental research topics that address central aims of WITS. These include examination of HLA antigens, TH1/TH2 lymphocyte "balance", apoptosis and syncytium forming viral isolates on the risk of vertical transmission or rapid disease progression. Other studies will examine virus in fetal tissue by in situ PcR and compare maternal-fetal viral envelope sequences to better define the stage of pregnancy at which infection occurs. In addition, the group proposes examining the feasibility of doing vaccine studies in pregnant women. These developmental research topics relate directly to the specific aims of WITS and make use of data and samples already available or samples that can be readily incorporated into the WITS-II protocol. The proposed plan will continue the work of the Chicago team in WITS-II. The innovative characteristics, quality of work and efficiency of the group will enhance the overall scientific productivity of WITS-II.